Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway

Abstract

Aim: Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Methods: Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg -1 ·d -1, po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. Results: DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Conclusion: Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

Reduced HMGB 1-Mediated Pathway and Oxidative Stress in Resveratrol-Treated Diabetic Mice: A Possible Mechanism of Cardioprotection of Resveratrol in Diabetes Mellitus

“…In this investigation, TLR4 expression and ROS production were upregulated in DM mice compared to normal mice. Consistent with the findings, TLR4 as well as ROS was upregulated in diabetic hearts, suggesting the critical role of ROS/TLR4 in DCM [33, 34]. More importantly, the expression of HMGB 1/RAGE/TLR4 and cardiac fibrosis were attenuated by administration of resveratrol, supporting the previous observation that resveratrol inhibited RAGE and TLR 4 dependent pathways [35, 36].…”

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

“…These alkaloids have been found to show a variety of pharmacological activities, including anti‐inflammatory, ‐viral, ‐fibrotic, and ‐cancer properties. According to our and others’ previous studies, the antioxidative and cardioprotective activities of matrine were featured 18, 19, 20. Several previous studies indicated that matrine regulated some protein kinases, such as AMP‐activated protein kinase and Janus‐activated kinase 21, 22.…”

Effect of procyanidine on VEGFR-2 expression and transduction pathway in rat endothelial progenitor cells under high glucose conditions

“…Several studies (Kanikarla-Marie and Jain, 2015;Liu et al, 2015;Seebacher et al, 2015;Wang et al, 2015) have reported that high glucose concentrations lead to over-aggregation of ROS in the body, which results in oxidative stress injury and affects the cell growth and survival cycle. This causes abnormal metabolism and dysfunction in cells, as well as apoptosis, ultimately resulting in diabetic vascular complications, ischemic necrosis, ischemic neuropathy, and paresthesia in the affected limbs.…”

“…AKT activates IkB kinase to promote IkB phosphorylation and degradation, causing the separation of IkB from NF-kB. Subsequently, NF-kB is transported to the nucleus, where it regulates transcription, thereby promoting cell proliferation and survival (Liu et al, 2015). We observed no significant difference in the expression of IkB-a between Con and Con + OPC EPCs (at all time points); on the other hand, IkB-a expression in the HG + OPC group was significantly lower than that in the HG group, further confirming that proanthocyanidins may alleviate the oxidative damage caused by high glucose in EPCs.…”

“…EPCs were isolated, cultured, and identified using methods previously reported in literature (Liu et al, 2015).…”